EP3303544B1 - Système de bioréacteur et procédé associé - Google Patents

Système de bioréacteur et procédé associé Download PDF

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Publication number
EP3303544B1
EP3303544B1 EP16711523.7A EP16711523A EP3303544B1 EP 3303544 B1 EP3303544 B1 EP 3303544B1 EP 16711523 A EP16711523 A EP 16711523A EP 3303544 B1 EP3303544 B1 EP 3303544B1
Authority
EP
European Patent Office
Prior art keywords
disposable bag
bioreactor system
receptacle
outlet opening
bioreactor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP16711523.7A
Other languages
German (de)
English (en)
Other versions
EP3303544A1 (fr
Inventor
Bernward Husemann
Simon Topp-Manske
Björn NICKEL
Marco LEUPOLD
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sartorius Stedim Biotech GmbH
Original Assignee
Sartorius Stedim Biotech GmbH
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Filing date
Publication date
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Publication of EP3303544A1 publication Critical patent/EP3303544A1/fr
Application granted granted Critical
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/14—Bags
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/26—Conditioning fluids entering or exiting the reaction vessel
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/22—Transparent or translucent parts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/26—Constructional details, e.g. recesses, hinges flexible
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/28—Constructional details, e.g. recesses, hinges disposable or single use
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/38—Caps; Covers; Plugs; Pouring means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/48—Holding appliances; Racks; Supports
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02—Stirrer or mobile mixing elements
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature

Definitions

  • the invention relates to bioreactor systems for receiving a disposable bag and a method for receiving a disposable bag into a bioreactor system.
  • Bioreactor systems also called bioreactors, and pallet tanks serve as a means for receiving and storing biological media, e.g. Fluids.
  • biological media may be provided in disposable bags, which may comprise a volume of several hundred liters. The biological media are introduced into the bioreactor within a disposable bag, in which they are heated to a predeterminable temperature over a predetermined period of time, usually several hours duration. In such a bioreactor, different studies can be made on the biological medium.
  • the handling of a bioreactor is usually carried out in a sterile environment, so that particularly high demands are placed on the quality assurance of the bioreactor. Furthermore, the handling of the partially heavy disposable bag and the operation of the bioreactors can be complicated and cumbersome.
  • WO 2008/135991 A2 relates to a large bioreactor with a support structure for receiving a bioreactor with multiple gas inlets and collecting ports. All gas inlets and collection ports are routed through the support structure.
  • the invention has for its object to improve the operation and / or handling of a bioreactor system of the type mentioned.
  • a first aspect relates to a bioreactor system for receiving a disposable bag with a receptacle for receiving the disposable bag, wherein a Bottom surface of the receptacle for supporting the disposable bag is formed in the receptacle. In the bottom surface, an outlet opening tapering downwards in the frame of reference of the earth for accommodating an emptying connection of the disposable bag that is complementary to the outlet opening is arranged.
  • the bioreactor system may be formed as a bioreactor, pallet tank and / or stirred tank reactor of the type mentioned, which can be designed to receive disposable bags with a volume of 1 liter up to about 2000 liters, in particular with a volume of 200 liters to 1000 liters.
  • the system can be designed, in particular, for receiving disposable bags in which there is a biological medium, such as a fluid, which is to be stored, tempered and / or differently examined in the system over a predetermined period of time.
  • the receptacle of the system provides a container interior that is configured to receive the disposable bag.
  • the receptacle for receiving a predeterminable type of disposable bag may be formed, so for example, a disposable bag of a predeterminable manufacturer and / or with a pre-definable filling volume.
  • receptacle for receiving a disposable bag is formed with a discharge port with a predeterminable shape.
  • Container walls of the receptacle define the container interior.
  • the container walls of the receptacle must not completely surround the container interior and / or limit.
  • the receptacle may have at its upper edge a stirring opening through which a stirring device can be connected to the disposable bag in the container interior.
  • the stirring device may be formed as a drive, which can be connected to a stirring rod, which is arranged in the interior of the disposable bag.
  • a stirring device is preferably formed at the upper end of the receptacle.
  • the receptacle can thus be designed in particular without cover and / or open at the top.
  • top, bottom, side, vertical, “horizontal”, “height” etc. refer to in the context of this invention to the reference system of the earth, in which the bioreactor system is arranged in an operating position.
  • the disposable bag is preferably placed in the receptacle so that it rests on a bottom of the receptacle and is in direct, physical contact with the container walls of the receptacle, in particular in contact with the bottom surface of the receptacle and optionally the container walls adjacent the bottom surface. While the biological medium in the receptacle is being examined, the disposable bag is supported by the bottom surface.
  • the medium can be at least partially discharged from the receptacle.
  • the contents of the disposable bag is emptied while the disposable bag is still placed in the receptacle.
  • the outlet opening is formed, through which the biological medium can be discharged specifically.
  • the bottom surface may be funnel-shaped towards the outlet opening, whereby the disposable bag can be almost completely emptied.
  • the bioreactor system is designed and provided for receiving disposable bags with an emptying outward, ie in the direction of the bag interior away, tapering discharge port.
  • the emptying port is formed in the bag bottom of the disposable bag and protrudes at least partially out of the disposable bag, in the operating position down.
  • the discharge port is not formed in the form of a straight cylinder or a simple pipe, but at least partially has outer dimensions tapering in the direction away from the bag. Exactly to this special, to the outside (in operating position: downwards) tapered discharge connection, the outlet opening in the bottom surface is complementary and vice versa.
  • the bottom surface of the receptacle may be completely or at least partially sloping towards the outlet opening in order to assist and / or facilitate a sliding in of the complementary emptying connection into the outlet opening.
  • the downwardly tapering outer dimensions of the emptying connection and / or the downwardly tapering inner surfaces of the outlet opening act as sliding surfaces for aligning and arranging the emptying connection.
  • the emptying connection of the disposable bag can be guided to its outlet position at the end of a hose routed through the outlet opening to the outlet opening when it is introduced into the receptacle.
  • hoses and / or closures of sterile connectors can be formed and provided, which can also be guided by the bottom surface.
  • the sterile connectors themselves may be designed to be larger than the emptying connection.
  • the outlet opening of the bottom surface is formed as a passage, which allows both the inclusion of the discharge port of the disposable bag as well as the implementation of at least one tube and / or closure of a sterile connector. In this case, the outlet opening takes up the emptying connection without completely dropping it through the outlet opening.
  • the smallest inner diameter of the outlet opening is therefore smaller than the largest outer diameter of the complementary emptying Anschungsungsansch.
  • the outlet opening can be adapted exactly to the outer shape of the complementary emptying connection, irrespective of the size of the optionally present additional sterile connectors.
  • the outlet opening only the complementary emptying connection is stored, and possibly one (or more) additional tubing for the sterile connectors is performed.
  • the (or the) possibly present (s) Sterilkonnektor (s) can (can) below the outlet opening on the end of the hose (the hoses) be mounted. As a result, even sterile connectors can be used that are larger than the outlet opening.
  • the complementary discharge port of the disposable bag is securely stored and / or held in the downwardly tapering discharge port.
  • the emptying connection is self-aligning in the set position due to the coordinated shaping surfaces of the emptying connection and the outlet opening. This also applies to the position of a stirrer shaft, possibly centered on the emptying connection, for stirring the interior of the disposable bag. This leads to a safe and low-wear operation of the stirring shaft.
  • the discharge port For discharging the biological medium, the discharge port, e.g. while it is stored in the outlet opening to be opened.
  • This safe and efficient storage of the discharge port in the discharge port improves the handling of the bioreactor system, especially in the arrangement of the bulky disposable bag in the receptacle and the discharge of the biological medium. Just at the bottom of the receptacle of disposable bag is difficult to access. The simplified alignment simplifies the handling and especially the orientation in the receptacle clearly.
  • the outlet opening is at least partially downwardly substantially conical and / or substantially hemispherical and / or substantially tapering in the form of a semi-ellipsoid.
  • the shape of a cone, a hemisphere, a semi-ellipsoid or e.g. a combination of a cylinder with one of these forms is particularly well suited as a complementary discharge port which slides automatically and / or guided into the complementary opening tapered outlet opening.
  • the bioreactor system comprises a fixing element for fixing the complementary discharge port of the disposable bag in the Outlet.
  • the fixing element can be designed as a mechanical fixing element such as a fixing bolt, which can engage in a complementary engagement (such as a groove) in the emptying connection.
  • the lock and / or the fixing element can be screwed, welded and / or glued to the bottom surface.
  • the bioreactor system may include a sensor for detecting the opening state of the locking of the exhaust port.
  • the bioreactor system has a remote control for opening and / or closing the fixing element.
  • the remote control can be designed either as an electrical remote control or as a mechanical remote control.
  • a locking of the outlet opening can be easily operated, in particular without requiring visual contact to the possibly difficult to access outlet opening.
  • the opening state of the lock can be seen without the lock itself to see.
  • the remote control locks the fixing safely without direct actuation of the fixing. The space required for locking on the floor surface is reduced.
  • a mechanical remote control can have at least one operating rod which reaches up to the outlet opening and by means of which the fixing element can be closed and / or opened.
  • the control panel can be mechanically coupled to a locking ring, which is arranged around the outlet opening around and whose rotation by means of the operating staff controls a position of the fixing.
  • the control panel can be formed at least one meter long, so that the fixing element is easy to use.
  • the remote control by means of a Baudenzugs, a servomotor, a rod to be implemented pneumatically and / or hydraulically.
  • the emptying port that is complementary to the outlet port is designed as an independent component of the bioreactor system that can be fastened to a standard emptying port integrated in the disposable bag in such a way that the complementary emptying port tapers in a direction away from the bag interior of the disposable bag.
  • the complementary discharge port is secured to the standard discharge port prior to insertion of the disposable bag into the receptacle.
  • the standard emptying connection is usually tubular.
  • the complementary discharge port is placed around and / or attached to this standard discharge port.
  • any disposable bag can be aligned with the outlet opening of the bioreactor, with the aid of the complementary emptying connection, the arbitrary disposable bag can be converted into a disposable bag with downwardly tapering emptying port which is complementary to the outlet opening.
  • the complementary emptying connection can be designed as a disposable component or as a reusable component and is a component of the bioreactor system.
  • the complementary emptying connection is designed as a multipart component.
  • the emptying connection can in particular be designed in two parts and have two half-shells, which can be placed around the standard emptying connection.
  • the individual parts of which the emptying connection is composed can be aligned and / or fixed relative to one another by means of fixing elements integrated into the individual parts. These fixing elements may include magnets, a snap lock, a latch and / or alignment pins with complementary alignment openings.
  • a second aspect relates to a bioreactor system for receiving a disposable bag, comprising a receptacle for receiving the disposable bag and a disposable bag Essentially on an outer wall of the receptacle adjacent arranged working platform.
  • an accessible by an operator surface of the working platform is arranged about 80 cm to about 140 cm below an upper edge of the receptacle.
  • the bioreactor system may be formed as a bioreactor of the type mentioned.
  • the bioreactor system according to the second aspect is formed similarly to the bioreactor system according to the first aspect, and therefore, many or even all embodiments of the bioreactor system according to the first aspect may apply to the bioreactor system according to the second aspect, and vice versa.
  • a work platform is provided, on which an operator has a comfortable access to the upper edge and thus to the stirring opening at the head end of the receptacle.
  • additional devices such as. a filter, at least one sensor, at least one probe, at least one motor and / or similar devices can be arranged, which can operate the operator from the working platform.
  • lines can be arranged for additional zugebbare media on the upper edge, the inflow of the work platform is conveniently controlled and / or controlled.
  • the work platform is formed above the floor on which the bioreactor system is located in operating position.
  • the work platform is designed essentially as a walk-on surface, which is designed to allow at least one person or preferably at least two persons to enter, and thus withstands a payload of at least 80 kg or at least 160 kg.
  • the surface is essentially aligned horizontally.
  • the work platform is formed adjacent to an outer surface of the receptacle and thus can reach all the way to the receptacle. As a result, the operator can approach the receptacle, resulting in efficient and simple operation of the additional devices and / or the Stirring device on the upper edge of the receptacle allows.
  • the surface of the work platform is arranged about 80 cm to about 140 cm below the upper edge of the receptacle, preferably between about 80 cm to about 120 cm, more preferably between about 95 cm and about 110 cm below the upper edge of the receptacle.
  • the upper edge of the receptacle can be easily reached by operators of different body size. At the same time the distance is such that the center of gravity of most people is below the top, so the operator would not have to worry about accidentally fall into the receptacle.
  • the work platform is preferably located only on an outer surface of the receptacle, such as e.g. only at the back or front of the bioreactor system, and not formed circumferentially around the receptacle. This saves space and is sufficient for operation.
  • the use of an additional ladder for operating the bioreactor is rendered superfluous by the work platform; on the other hand, the operator on the work platform can approach all the way to the receptacle and can stand securely on the work platform. This significantly improves and simplifies the operation of the bioreactor.
  • the bioreactor system according to the second aspect may have all the additional features of the bioreactor system according to the first aspect and vice versa.
  • the bioreactor system has an integrated ladder leading from a floor on which the bioreactor system is placed in operating position to the walk-on surface of the work platform.
  • the ladder simplifies the walk-through of the work platform and eliminates the need for a separate ladder to climb the work platform.
  • the ladder may be in the form of multiple steps that are integrated into the bioreactor system.
  • the work platform has a railing that at least partially bounds the work platform.
  • the railing secures an operator on the work platform in at least one direction, e.g. away from the receptacle.
  • a railing is especially intended for work surfaces that are more than 65 cm above the ground. This makes the operation of the bioreactor system safer.
  • the surface of the work platform is arranged at a height of at most 65 cm above the ground, wherein the work platform is designed without railing.
  • the work platform On a low work platform can be dispensed with a railing, without limiting the security. As a result, the freedom of movement and thus the ease of use is increased.
  • the work platform is designed to be at least partially extendible and / or fold-out. This is particularly advantageous in a limited space, since here the bioreactor system can be made very compact and is better transportable.
  • One embodiment relates to a bioreactor system with a receptacle for receiving a disposable bag, wherein below the receptacle a collecting trough is arranged for collecting a fluid emerging from the receptacle.
  • a collecting trough is arranged for collecting a fluid emerging from the receptacle.
  • no medium should escape from the receptacle uncontrolled.
  • the collecting trough can catch escaping liquid before it flows onto the floor. This reduces both the risk of contaminating the soil and simplifying the removal of the leaked liquid.
  • the drip pan has a lining made of plastic and / or is adjustable in its exact position below the receptacle.
  • the height of the sump can be adjustable above the ground, for example to compensate for uneven ground.
  • the lining of the tub can either be designed as a firmly integrated plastic coating and / or as an insertable disposable bag.
  • the bioreactor system has at least system rail for attaching at least one additional device.
  • the system rail is used to attach an accessory device such as a a probe or to secure cables or other feeders.
  • an accessory device such as a a probe or to secure cables or other feeders.
  • the bioreactor system can be customized and tailored to specific applications.
  • the system rail may be standardized and / or at least 10 cm long.
  • the bioreactor system may include a window, e.g. have a viewing and / or probe window in the receptacle, to which the system rail is arranged adjacent.
  • the window is transparent and serves to observe and / or control the biological medium in the bioreactor.
  • the system rail may be arranged substantially parallel to the longitudinal axis of the window.
  • at least one system rail may be formed on an outer wall of the receptacle.
  • the system rail is seconded at a distance of about 3 cm to about 20 cm from the window spaced.
  • the distance specifications are the smallest distance of a part of the system rail from a part of the window.
  • the system rail may preferably be arranged as close to the window as possible to allow an arrangement of an additional device as close to the window.
  • the system rail is not further than about 20 cm, preferably not more than a maximum of 10 cm apart from the window.
  • the system rail is particularly advantageously placed for receiving at least one additional device that must be arranged at the window, such as a probe for determining relevant process parameters in the biological medium.
  • the bioreactor system has at least one system rail adjacent to the upper edge of the receptacle for attaching at least one additional device.
  • the individual attachment of additional devices is also adjacent to the upper edge, so adjacent to the stirring opening of the receptacle allows.
  • the system rail may be at least 10 cm long and / or arranged in a substantially horizontal direction approximately parallel to the upper edge of the receptacle.
  • a third aspect relates to a bioreactor system for receiving a disposable bag, comprising a receptacle for receiving the disposable bag and a cable guide on an outer wall of the receptacle, wherein the cable guide is formed to an upper edge of the receptacle.
  • the cable guide can also be designed as a hose guide or as a combined cable and hose guide.
  • the bioreactor system may be formed as a bioreactor of the type mentioned.
  • the bioreactor system according to the third aspect is formed similarly to the bioreactor system according to the first and / or second aspect, and therefore many or even all embodiments of the bioreactor system according to the first and / or second aspect may apply to the bioreactor system according to the third aspect, and vice versa.
  • a cable guide is provided on an outer wall of the receptacle, which is formed approximately to the upper edge of the receptacle.
  • the cable guide may be formed substantially U-shaped, with cables and / or tubes are introduced into the U-opening and guided there safely.
  • the cable guide may additionally or alternatively be at least partially formed as a grid cable channel.
  • the cable guide is designed to securely receive cables and / or tubing.
  • the cables and / or hoses are secured and guided in a fixed target position on the receptacle, whereby the probability of disturbing an operator by the Cable and / or hoses is reduced, as well as the risk of accidental decoupling of a cable and / or hose and / or a supply line.
  • the cable guide extends to the top of the receptacle and thus to the stirring opening.
  • power cables for a stirring motor and / or further supply lines for sensors must be routed right up to the stirring opening, which extend from above into the stirring opening.
  • further additional media containers can be arranged at the stirring opening, via which additional media can be fed into the receiving container.
  • leads or hoses can be performed to the additional media containers through the cable guides.
  • the cable routing reduces the risk of tripping.
  • the cable routing also reduces the risk of damage to the hoses and cables. This makes the operation of the bioreactor more user-friendly.
  • the bioreactor system according to the third aspect may have all the additional features of the bioreactor system according to the first and / or second aspect and vice versa.
  • the cable guide is at least partially meander-shaped.
  • the cable guide can have plug-in flaps which meander in front of a guide channel of the cable guide.
  • the cables and / or lines can be quickly and safely inserted behind the meandering plug-in flaps or arranged and are out there.
  • the bioreactor system has a support bridge which is arranged on the upper edge of the receptacle.
  • the support bridge is arranged at least at one point of the upper edge of the receptacle, leads to the cable guide.
  • On the support bridge can / can be arranged a stirring device and / or sensors of the bioreactor system.
  • the cable guide leads the cables and / or wires directly to at least one point of attachment of the support bridge, from where the cable or the lines are continued on the support bridge and the devices arranged there.
  • the bioreactor system has two such cable guides, which are formed substantially symmetrical to each other and which lead to the two attachment points of the support bridge on the upper edge of the receptacle.
  • the cable guide extends from the upper edge of the receptacle along its outer wall substantially vertically down to a Umschwenkddling at which the cable run from the outer wall of the receptacle to an outer region of the bioreactor system.
  • the cable guide extends at least partially substantially vertically, up to and / or away from the upper edge of the receptacle, ie in an upper region of the Biorekatorsystems.
  • the cable guide is at least in this upper area designed to save space and thus facilitates the operation or access to the stirring opening of the bioreactor system.
  • the cable guide leads away from the outer wall of the receptacle at the earliest at the pivot point, and thus at a region which is e.g. is located below the work platform and barely disturbs the access to the bioreactor.
  • this is formed in two parts with at least one permanent cable guide and at least one additional cable guide.
  • the separation in permanent and additional cable management allows on the one hand a fixed and secure guiding the permanently installed cables and / or lines, on the other hand a comfortable and safe installation of additional cables and / or cables that are application-specific and not always needed.
  • the bioreactor system has a darkening device for at least one viewing window and / or a darkening cover for darkening an opening at an upper edge of the receiving container.
  • a darkening device for example in the form of a roller blind, slider, an electrochromic disc of an electrically darkenable material, etc.
  • the darkening device uniform reaction conditions are possible and in particular reduces the risk of influencing the biological reaction by light.
  • the darkening cover which can be designed, for example, in the form of a tarpaulin and can be placed over the stirring opening.
  • the bioreactor system can be designed in particular as a bioreactor system according to the first aspect.
  • the complementary discharge port is formed as a separate component that is disposed on and / or around the standard discharge port of the disposable bag.
  • a hose is passed through the outlet opening, one hose end of which is attached to the complementary drainage connection.
  • the complementary emptying connection is guided with the aid of the hose into the downwardly tapering outlet opening, for example by the hose being pulled downwards through the outlet opening and with it the complementary emptying connection into the outlet opening.
  • the method according to the fourth aspect simplifies and improves the alignment and introduction of any disposable bag with any standard emptying port into the bioreactor system.
  • FIG. 1 shows a perspective view of a device 1 for receiving a disposable bag.
  • the device 1 shown in the figures can be designed as a component of a system and / or as a bioreactor system for receiving a disposable bag.
  • the device 1 has a receptacle 10, which has substantially the shape of a vertically arranged cylinder, that is, whose cylinder axis is arranged substantially vertically.
  • the receptacle 10 has a container interior into which a disposable bag 44 (see FIG. 3 ), which may include, for example, a biological medium.
  • the biological medium in the disposable bag 44 is stored in the container interior of the receptacle 10 over a specific (predetermined or predeterminable) period of time. While the disposable bag 44 containing the biological media is located within the receptacle 10, different reactions may occur with or on the biological media.
  • the device 1 can also be designed as a bioreactor and / or bioreactor system.
  • the device 1 has two bottom windows 12 in the lower third, as well as a door view window 32.
  • the bottom windows 12 can be used to insert at least one probe and / or at least one tube into the disposable bag.
  • the door view window 32 is preferably formed substantially in the form of an elongated rectangle, with their longer sides being substantially vertically aligned.
  • the door view window 32 is preferably formed approximately in the center of a single-leaf door 30 in the container wall of the receptacle 10.
  • FIGS. 2A and 2B show together with FIG. 1 different views of the device 1. So, for example, shows FIG. 2B a frontal side view of the single-leaf door 30.
  • the single-leaf door 30 extends in width, ie in the horizontal direction, approximately over a lateral surface or cylinder segment of the receptacle 10 from about 70 ° to about 160 ° (eg from about 100 °) , In the horizontal direction, the single-leaf door 30 preferably extends from two door hinges 34 along the cylinder jacket to a door handle 35 at the opposite door end.
  • the single-leaf door 30 is preferably formed substantially in the upper half, more preferably in the upper two-thirds of the receptacle 10, while the lower half (preferably the lower third) of the receptacle 10 is preferably formed substantially in the form of a rigid bottom shell, which itself is not openable.
  • the single-leaf door 30 is rotatable about the door hinges 34 and thus can be opened. If the single-leaf door 30 is open, then a door opening is formed in the receptacle 10 at a lateral position, by which access to the container interior of the receptacle 10 is made possible.
  • the disposable bag 44 can preferably be introduced into the container interior of the receiving container 10 from a substantially lateral or radial direction, that is, essentially in a horizontal direction of movement.
  • a darkening device in the form of a Schoverdunklung 33 is preferably arranged, which can be folded in front of the door window 32, pushed, rolled or otherwise used to darken the door view window 32.
  • the Matverdunklung 33 serves to darken the container interior.
  • a similar or otherwise formed (ground) obscuration can preferably also be provided for the bottom windows 12 and possibly further viewing windows.
  • the device 1 is mounted rollably on rollers 18 on which the device is mounted e.g. can be pushed through a room.
  • the device 1 at the lower end of Fixierfoue 19 have, which serve for fixing and adjusting the height of the device 1.
  • the fixing feet 19 can also be used to compensate for uneven ground.
  • a collecting trough 15 is arranged, which is open at the top and for at least partial collection of an optionally exiting from the container interior biological medium and / or a tempering medium is used.
  • the drip pan 15 may preferably have a lining made of plastic, which is adapted to the dimension of the drip pan 15. As a result, the entire device 1 is protected, in particular possibly existing weight cells and / or load cells. Furthermore, the lining improves biosecurity, e.g. by simply removing contaminating biomaterial from the sump 15 instead of subsequently purifying it.
  • the drip pan 15 is adjustable by an adjusting device.
  • the relative height of the collecting trough 15 can be adjusted by means of the adjusting device and / or the orientation below the receiving container 10.
  • one or more system rails 17 Adjacent to the floor windows 12 and / or the door viewing window 32, one or more system rails 17 may be disposed on the device 1, to which one or more ancillary equipment (such as probes and / or other fixtures for specialized equipment such as sampling systems, hoses, or other such mechanical Releasable connections) with the disposable bag connectable and / or attachable are.
  • one or more substantially horizontally extending system rails 17 are arranged adjacent to the floor windows 12, and preferably in each case one system rail 17 above and below each floor window 12.
  • the receptacle 10 is formed substantially open at the top. Instead of a cylinder cover or independently thereof, the receptacle 10 has a stirring opening, which is preferably formed at or near the upper edge of the receptacle 10. Above the upwardly open receiving container 10, a stirring device 14 is formed or arranged, via which a stirring rod through the stirring opening can be connected to the disposable bag 44 so that the interior of the disposable bag 44 can be mixed.
  • the stirring rod can be arranged inside the disposable bag and be connected via a coupling or coupling with the stirring device 14.
  • the stirring device 14 is preferably formed centrally above the receptacle 10 and is supported by a support bridge 14A-C which rests on or on an upper edge of the receptacle 10 on substantially opposite side walls of the receptacle 10.
  • the support bridge has one or more support members 14C extending from at least one side wall of the receptacle 10 at least partially over the upper opening thereof.
  • two support elements 14C are provided, which extend transversely across the receptacle 10 and are supported on approximately opposite areas on the receptacle 10 and are supported by this.
  • the two support members 14C are interconnected by one or more (eg, two) cross members 14B.
  • a stirring element receptacle 14A is provided, to which stirring elements of the stirring device can be attached, in order to mix or stir the contents thereof via the stirring rod through the stirring opening of the disposable bag 44.
  • a motor 14D is attached to the stirring element receptacle 14A, which drives the stir bar.
  • the two support elements 14B and / or the stirring element receptacle 14A are formed like cheeks that laterally protect the motor 14D so that it is protected against, for example, accidental collision with external objects (eg a support crane).
  • the stirring element receptacle 14A and / or a or a plurality of support elements 14C have a support region 14E above the receptacle 10 or the disposable bag 44, to which one or more additional processing means (eg filter, safety valve (s) and / or sensor (s)) can be arranged, by means of which the contents of the disposable bag Can be processed and / or analyzed and / or in a specific (predetermined or predeterminable) state (eg, temperature, pressure, CO 2 content and / or O 2 content) held or offset.
  • a specific (predetermined or predeterminable) state eg, temperature, pressure, CO 2 content and / or O 2 content
  • FIG. 2A shows a side view of one of the two cable guides 13.
  • the second of the two cable guides 13 is disposed on the opposite outer wall of the receptacle 10.
  • the side view of FIG. 2A shows the device 1 in a position opposite to the side view of FIG. 2B rotated by 90 °.
  • the cable guide 13 has an upper cable guide 13E, which extends substantially vertically from the upper edge of the receptacle 10 downwards, at least to half the height of the receptacle 10, namely up to a Umschwenkddling 13A. From Umschwenkddling 13A on the cable guide 13 continues as a sub-cable guide 13 B side and / or back away.
  • the vertical part of the cable guide 13 (ie, the upper cable guide 13E) has one or more plug-in flaps 13D behind which (or outside) cables and / or cables can be plugged or arranged such that the cables and / or cables are both from the outer wall of the receptacle 10 towards the inside, as well as outwardly guided by the plug-in flap (s) 13 D and / or held securely.
  • the plug-in flaps 13E engage in a meandering manner (or laterally alternately) in front of the upper cable guide 13E, so that the cable guide 13 is preferably at least partially substantially meander-shaped.
  • the cable guide 13 may have molded components into which the one or more cables and / or one or more hoses and / or one or more lines can be arranged or inserted. Furthermore, the cable guide 13 may preferably have at least one strain relief. The cable guide 13 reduces the risk of unwanted interaction of a user (eg a trip hazard) and thus increases safety with improved handling.
  • FIG. 3 shows in a perspective view a view of a vertical section through the device 1.
  • a disposable bag 44 more precisely a section through this disposable bag 44, which is arranged in the container interior of the receptacle 10.
  • a biological medium 42 is arranged, which is filled to the level of a predetermined level 40 level.
  • the biological medium 42 extends from the bottom of the receptacle 10 to a level 40 and thus preferably fills the entire internal volume of the receptacle 10 up to the level 40, minus the volume of the walls of the disposable bag 44, which are very thin and hardly fall into the weight.
  • the disposable bag 44 is supported by a container wall 16 of the receptacle 10 or held substantially in the form, which preferably extend from a rounded bottom surface 11 of the receptacle 10 to above the level height 40 also upwards.
  • the bottom surface 11 may be formed to support the disposable bag 44.
  • the container wall 16 may extend vertically upward in a substantially vertical direction.
  • a tempering wall or tempering hollow wall 20 is arranged, in which a (not shown in the figures) tempering is or can be arranged.
  • the temperature control medium is preferably regulated to a low pressure of less than 1 bar or less than 0.5 bar.
  • the tempering hollow wall 20 extends over the entire bottom of the Receiving container 10 and along the container walls of the bottom surface 11 at up to above the level 40 addition.
  • the biological medium 42 is (preferably in direct heat contact) to the tempering hollow wall 20 and is brought into thermal contact with this, from which it is preferably separated only through the thin bag wall of the disposable bag 44.
  • About the tempering the biological medium can be controlled to a predeterminable temperature.
  • the device 1 can in particular be designed and provided to temper the container interior to a specific (predetermined or predeterminable) temperature.
  • the Temperierhohlwand 20 is at least partially surrounded on its outer side by a Isolierhohlwand 25, in which preferably an insulation (eg PU foam or vacuum) is located.
  • the Isolierhohlwand 25 surrounds the container interior of the receptacle 10 preferably almost completely from the bottom of the receptacle 10 to the upper end of the container wall 16 (see also FIG. 3 ).
  • the Isolierhohlwand 25 isolates both the container interior, and in particular the tempering hollow wall 20 to the outside.
  • the insulation arranged in the insulating hollow wall 25 provides directional tempering by means of the tempering medium towards the interior of the container, which increases the energy efficiency of the device 1.
  • the tempering medium is preferably located in the interior of a closed tempering system, which comprises the interior of the tempering hollow wall 20.
  • the regulation and / or control of the temperature of the temperature control can be done via an internal, electrically operated heater and optionally or alternatively via an external heat exchanger. Both cooling and heating of the temperature control medium can take place independently of the internal electrical heating device of the temperature control system via the external heat exchanger.
  • the disposable bag 44 is e.g. after completion of the biological reaction by an arranged below the device 1 outlet port 5 at least partially emptied and can then be disposed of completely.
  • an emptying connection 45 of the disposable bag 44 is mounted or provided in the outlet opening 5, via which the disposable bag 44 can be emptied.
  • the outlet port 5 is formed in the bottom surface 11 of the receptacle 10.
  • FIG. 4A shows a side view of a device 2 for (at least partially) receiving a disposable bag with a (especially high or elevated) working platform 60.
  • the device 2 may be formed in particular as a bioreactor and / or bioreactor system for receiving a disposable bag.
  • the working platform 60 On one side of the bioreactor 2, the working platform 60 is formed, on which an operator 100 stands and operates the stirring device 14. Furthermore, the operator 100 has access from the work platform 60 to one or more sensors formed at the agitation port of the bioreactor 2.
  • the work platform 60 has a walk-on surface on which the in FIG. 4A shown operator 100 stands or can stand.
  • This surface of the work platform 60 is arranged and designed as a high work platform, is preferably at least about 65 cm from the ground, for example, at a height of about 118 cm.
  • the walk-on surface of the work platform is located immediately adjacent to the receptacle 10 and preferably at least about 40 cm (eg about 45 cm) wide.
  • the walk-on surface extends away from the receptacle 10 (preferably over a width of about 45 cm) to a platform end facing away from the receptacle 10.
  • a railing 62 is formed, which protects the operator 100 from falling from the accessible surface.
  • FIG. 4B shows a side view of a device 3 for receiving a disposable bag with a (preferably low) working platform 60.
  • the device 3 may be formed as a bioreactor and / or bioreactor system for receiving a disposable bag.
  • the low work platform 60 of the device 3 is similar to that of FIG FIG. 2 shown device 2 is formed. However, the low working platform 60 of the device 3 is preferably arranged only about 30 cm to about 64 cm above the ground and is preferably designed without railing.
  • the darkening serves (preferably together with the door darkening and / or the two floor window darkening) to control and / or control the incidence of light into the container interior.
  • FIG. 5 shows a perspective view of a two-piece conical evacuation port 45.
  • the emptying port 45 is configured and provided to be laid to a standard emptying port of a disposable bag 44 to give the emptying port of the disposable bag 44 a conical outer surface.
  • the discharge port 45 is preferably formed as a separate component and may be formed as a component of a bioreactor system, such.
  • the emptying port 45 is preferably formed in two parts and has a first sub-shell 45A, and a second sub-shell 45B.
  • the two subshells 45A and 45B are formed substantially equal in size and are configured and intended to be assembled to form the composite exhaust port 45.
  • Each of the two partial shells 45A and 45B is preferably formed as a half-cone, with a tapered, substantially conical outer side and / or a substantially straight cut surface inside, in which a Recording 48 is formed.
  • the receptacle 48 is formed substantially in the form of a hollow cylinder and serves to receive a standard emptying connection of a disposable bag.
  • the cut surface inner sides of the two partial shells or half shells 45A and 45B are designed and intended to be placed flat on one another. So assembled, the (preferably substantially cone-shaped) evacuation port 45 is provided.
  • the first subshell 45A has one or more (e.g., two) alignment pins 46A formed on the cut surface inner side and approximately perpendicular to the cut surface inside.
  • the one or more (e.g., two) alignment pins 46A are configured and intended to be at least partially inserted into one or more (e.g., two) complementary alignment apertures 46B of the second sub-shell 45B, thereby correctly aligning the two sub-shells.
  • one or more magnets 47A and 47B which attract each other and / or contract or hold together the two sub-shells 45A and 45B, are preferably arranged on the cut surface inner sides.
  • the two partial shells can have one or more hinges or hinges with which they can be folded together securely into a desired position.
  • Draining connection 45 shown preferably has a substantially cone-shaped, cylindrically symmetrical outer surface.
  • the outer surface of the emptying port may also be formed substantially hemispherical and / or in the form of a semi-ellipsoid. Decisive in the outer shape is merely that the emptying port in its assembled form tapers in one direction (preferably cylindrically symmetrical), in a direction that points away from the interior of the disposable bag in the operating position.
  • FIG. 6A shows in a plan view the in FIG. 5 shown two-piece conical discharge port 45 in an assembled form.
  • the centrally arranged receptacle 48 is clearly shown, in the axial direction along the axis of the Hollow cylinder, as the receptacle 48 is formed.
  • the emptying port 45 is substantially circular, wherein the receptacle 48 is formed in the center of the circle.
  • FIG. 6B shows a cross section through the in FIG. 5 On the left, only the first subshell 45A is shown in the cross section, while on the right, a cross section through the second subshell 45B is shown, perpendicular to the plane of the inner surface of the intersection.
  • the emptying port 45 is preferably formed substantially cylindrically symmetrical with respect to a central axis, which coincides with the cylinder axis of the receptacle 48.
  • the emptying port 45 has at the upper end to a flange or a circular disc 50 which from the top in FIG. 6A is shown.
  • the outer surface of the emptying port 45 tapers along a first sliding surface 51 and a second sliding surface 52, between which a circumferential groove 53 is formed in the outer surface.
  • the first sliding surface 51 is formed below the circular disk 50, the circumferential groove 53 below the first sliding surface 51, and the second sliding surface 52 below the circulation groove 53.
  • the circulation groove 53 may be arranged below a long sliding surface.
  • FIG. 6C shows in a cross section the two-part conical discharge port 45 in an operating position in which it is placed around a standard emptying port 200.
  • the emptying port 45 is placed or arranged with its two half-shells substantially around the standard emptying port 200 of a commercially available disposable bag 44 that the disposable bag 44 now has the cone-shaped emptying port 45 as its emptying port, in particular exactly downwardly tapering outer dimensions.
  • the standard emptying connection 200 is arranged in the hollow cylindrical receptacle 48 in such a way that the substantially cylindrical standard emptying connection 200 is formed by means of a recirculating projection 49 in the hollow cylindrical receptacle 48 Recording 48 is held.
  • the recirculating projection 49 is formed as part of the emptying port 45 in the receptacle 48 at each of the two subshells 45A and 45B.
  • the circulation projection 49 has approximately perpendicularly into the interior of the hollow cylinder, that is perpendicular to the cylinder axis of symmetry of the emptying port 45, and serves to engage in a corresponding recess in the standard emptying port 200, as in Fig. 6C shown.
  • the depression in the standard emptying port 200 can usually be used to connect a hose or the like. be educated.
  • the two subshells 45A, 45B are held firmly and stably about the standard emptying port 200 of the disposable bag.
  • the partial shells can also be arranged around the standard emptying connection 200 of the disposable bag by means of a snap closure or other fixing means.
  • the one-way bag 44 thus provided with the emptying port 45 can be introduced into one of the devices 1, 2 or 3, for example, in the FIGS. 1 to 4 are shown.
  • the receptacle 10 has a bottom surface 11, in which a downwardly tapering outlet opening 5 is formed, as already in Fig. 3 small and as an enlarged detail in Fig. 6C shown.
  • the outlet opening 5 is preferably formed substantially cylindrically symmetrical about a vertical cylinder axis and has downwardly tapering inner surfaces which is formed as seating surfaces 6 for the outer surfaces of the emptying port 45.
  • the seat surfaces 6 are formed substantially complementary to the outer dimensions of the emptying port 45 and / or substantially matched to the taper of the first and second sliding surfaces 51 and 52 and adapted to this. In particular, the slopes are matched to each other in cross section. In other words, the decrease of the inner radius along the axis of symmetry of the exhaust port 5 downward is equal to the decrease of the outer radius along the symmetry axis of the exhaust port 45 downward.
  • the seats 6 thus have substantially the shape of a down tapering cone on.
  • the discharge port 45 slips or slides without much action of an operator, so practically by itself, in the outlet opening 5 in the bottom surface 11 of the receptacle.
  • the emptying port 45 can be guided at a hose or cord end into the receiving opening 5.
  • the emptying connection 45 together with the enclosed standard emptying connection 200 slips so far into the outlet opening 5 until the flange or the circular disk 50 rests on the outlet opening 5.
  • the circular disk 5 has an outer diameter that is larger than the inner diameter of the outlet opening 5 is formed. Therefore, the flange or disc 50 is in the in FIG. 6C shown operating position flat on the bottom surface 11, centered about the axis of symmetry of the outlet opening 5.
  • At least one fixing element 7 is preferably arranged in the form of a bolt, which engages in a closed position at least partially in the circulation groove 53 of the emptying port 45 and fixes it in the outlet opening 5.
  • the fixing element 7 is preferably movable approximately perpendicular to the central axis (ie the axis of symmetry) of the outlet opening 5 between a closed position and an open position. By the fixing element 7, a locking of the outlet opening 5 is provided.
  • FIG. 6C is the closed position of the lock, so the fixing 7, shown, in which the emptying port 45 is fixed by means of the fixing element 7 in the outlet opening 5 in the operating position.
  • the fixing element 7 can be opened and closed by means of a remote control 70.
  • This remote control 70 is designed as a mechanical remote control, which in FIG. 6C only partially shown, but more specific in the Figures 7A-7C ,
  • FIG. 7A shows in a bottom view (ie in a view from below vertically upward) the downwardly tapering outlet opening 5 with the fixing element 7 open and with the associated mechanical remote control 70.
  • the remote control 70 is actuated by means of a handle 71 on which a horizontal bar 72 is arranged can be, which is movable in an eyelet 73 to a stop 76 in a substantially horizontal direction.
  • FIG. 7C shows the remote control 70 in a side view.
  • the handle 71 In the in the FIGS. 7A and 7C shown open position of the latch, the handle 71 is maximally moved away from the outlet opening 5.
  • the handle 71 is disposed at an end of the horizontal bar 72 facing away from the outlet port 5.
  • An opposite end of the horizontal bar 72 is formed as a hinge 75.
  • a vertical rod 74 In this joint 75, a vertical rod 74 is arranged, which is fixed to a rotary ring 8.
  • the vertical bar 74 is preferably oriented substantially vertically and thus is approximately perpendicular to the horizontal bar 72, which is preferably arranged substantially horizontally.
  • the vertical bar 74 may be shorter than the horizontal bar 72.
  • the vertical bar 74 may be dispensed with in an alternative embodiment, especially in otherwise accessible bioreactor systems.
  • the rotary ring 8 is rotatably mounted around the outlet opening 5, more precisely about a fixing ring 9 (see FIG. 7A ).
  • the rotary ring 8 is rotatable about the vertical center axis (ie the axis of symmetry) of the outlet opening 5, between the closed position and the open position. The latter is in the FIGS. 7A and 7C shown.
  • the fixing ring 9 is arranged around at least a part of the outlet opening 5 around, immovable in its position and serves as an inner rotary armature about which the rotating ring 8 arranged outside is rotatably mounted.
  • the device can have a slide with which the emptying connection 45 can be locked in or at the outlet opening 5.
  • the fixing element 7 has a suspension which presses the fixing element 7 radially away from the center axis of the outlet opening 5 to the outside, in the open position into the recess 8A in the rotary ring 8. Pressed outward, the fixing element 7 no longer protrudes into the interior of the outlet opening 5, but closes substantially flush with the seating surfaces 6 of the outlet opening 5, thereby releasing essentially the entire outlet opening 5.
  • FIG. 7A The exact position of the rotary ring 8 relative to the fixing ring 9, and in particular the engagement of the fixing element 7 in the recess 8A, is in FIG. 7A shown again in an enlarged section.
  • the cone-shaped discharge port 45 of a disposable bag can slide unhindered into the outlet opening 45.
  • FIG. 7B The closing position in which the fixing element 7 projects in the direction of the central axis into the interior of the outlet opening 5 is in FIG FIG. 7B shown.
  • the handle 71 of the remote control 70 is moved towards the outlet opening.
  • the horizontal rod 72 is moved through the fixed eyelet 73 until the stop 76 abuts the eyelet 73.
  • the stopper 76 is formed larger than the eye opening of the eyelet 73.
  • the joint 75 and thus also the vertical rod 74 is moved in the direction away from the handle 71.
  • the rotary ring 8 rotates about the fixing ring 9.
  • the recess 8A is moved relative to the fixing element 7, namely away from it.
  • the recess 8A is thus preferably arranged offset relative to the fixing element 7.
  • the rotation of the rotary ring 8 from the open position to the closed position can be carried out over a rotation angle of about 20 ° to about 60 °, in the embodiment shown in the figures over a rotation angle of about 40 °.
  • the rotary ring 8 rotates back until the recess 8A is again arranged at the level of the fixing element 7, which jumps into the recess 8A and blocks the further rotational movement.
  • the fixing element 7 thus serves at the same time as limiting the opening movement, while the stop 73 formed around the horizontal rod 72 limits the closing movement.
  • the remote control 70 facilitates fixing the emptying port 45 in the outlet port 5 to the hard-to-reach bottom surface 11 of the receptacle 10.
  • a disposable bag with an already integrated (preferably cone-shaped) emptying port can be used for introduction into the bioreactor system.
  • the emptying connection can also be made up of more than just two components, and / or instead of (or in addition to) the magnets, mechanical fixing devices, such as latching hooks etc., can be provided.
  • the locking mechanism of the outlet opening can be used not only for locking the emptying port, but also for fixing any other port of the disposable bag in another bag position.
  • the emptying connection can also be fixed by means of a sliding mechanism engaging in the circumferential groove.
  • Figures 8A and 8B show in a side view and in a perspective view of a device 1 'for (at least partially) receiving a disposable bag with a working platform 60.
  • the device 1' may be formed in particular as a bioreactor and / or bioreactor system for receiving a disposable bag.
  • the working platform 60 On one side of the bioreactor 1 ', the working platform 60 is formed, on which an operator 100 stands and operates the stirring device 14. Furthermore, the operator 100 has access from the work platform 60 to one or more sensors formed at the agitation port of the bioreactor 1 '.
  • the work platform 60 has a walk-on surface on which the in the Figures 8A and 8B shown operator 100 stands or can stand. This surface of the work platform 60 is arranged and designed as a work platform.
  • the walk-on surface of the work platform is arranged adjacent to the receptacle 10 and preferably at least at one corner of the device 1 'at least about 40 cm wide.
  • the walk-surface extends from the receptacle 10 away to a receptacle 10 facing away from the platform end.
  • the work platform 60 is formed as a tread that the operator 100 can enter to more easily access the agitator 14 and / or associated motor.
  • the work platform 60 is formed as a walk-surface, for example, rests directly on the sump 15 and / or attached to the sump 15, in particular on or at an upper edge of the sump 15. This allows the work platform 60 is particularly inexpensive, inexpensive and / or space saving implemented.
  • the drip pan 15 is in this case designed so that the receptacle 10 is in the drip pan 15. Furthermore, the rollers 18 and / or the Fixierfoue 19 of the device 1 'are formed so that they are embedded in the drip pan 15 and / or integrated.
  • the sump 15 is compared to those in the FIGS. 4A and 4B shown embodiments, so to speak "lowered", whereby the overall height of the device 1 'can be reduced. This can be achieved in that the rollers 18 and / or the Fixierfpune 19 at least partially attach to an upper edge of the sump 15 and / or attached to this upper edge, and thus either no or only a reduced space below the sump 15 need.
  • rollers 18 may be arranged at corners of the collecting trough 15, which protrude laterally from the receptacle 10 and therefore need not have a collecting volume. At these positions, the sump 15 can thus be arranged sufficiently spaced from the ground, which provides sufficient space for the rollers 18.
  • the collecting tray 15 may have a collecting volume that extends to near the bottom.
  • the drip pan 15 can be arranged below the receptacle 10 at a maximum distance of about 5 cm from the ground, preferably at most about 3 cm, more preferably at most about 1 cm apart.
  • the overall height of the device 1 ' can be reduced, and at the same time an accessibility of the stirring device 14 and / or the associated motor for the operator 100 can be improved.
  • the design of the work platform 60 as a relatively low footboard on the lowered tray 15 also makes it possible to dispense with a railing 62 of the work platform 60, as for example in the raised work platform 60 in Fig. 4A is shown. This is a component cost in the production of Device 1 'reduced.

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Claims (15)

  1. Système de bioréacteur (1 ; 2 ; 3) destiné à recevoir un sac jetable (44), doté
    d'une cuve collectrice (10) servant à recevoir le sac jetable (44),
    dans lequel
    une surface de fond (11) de la cuve collectrice (10) est conçue pour soutenir le sac jetable (44) dans la cuve collectrice (10) et
    un orifice de sortie (5) se rétrécissant vers le bas dans le système de référence terrestre est disposé dans la surface de fond (11) pour recevoir un raccord d'évacuation (45) du sac jetable (44), complémentaire de l'orifice de sortie (5).
  2. Système de bioréacteur selon la revendication 1, dans lequel l'orifice de sortie (5) se rétrécit au moins en partie vers le bas sous une forme sensiblement conique et/ou sous une forme sensiblement hémisphérique et/ou sous une forme sensiblement semi-ellipsoïdale.
  3. Système de bioréacteur selon l'une des revendications 1 ou 2, doté d'un élément de fixation (7) pour attacher le raccord d'évacuation (45) complémentaire du sac jetable (44) dans l'orifice de sortie (5).
  4. Système de bioréacteur selon la revendication 3, doté d'une télécommande (70) pour ouvrir et/ou fermer l'élément de fixation (7).
  5. Système de bioréacteur selon l'une des revendications précédentes, dans lequel le raccord d'évacuation (45) complémentaire de l'orifice de sortie (5) est conçu comme un composant à part entière du système de bioréacteur (1 ; 2 ; 3), qui peut être fixé à un raccord d'évacuation standard (200) intégré au sac jetable (44), de sorte que le raccord d'évacuation complémentaire (45) se rétrécit dans une direction, qui s'éloigne de l'intérieur du sac jetable (44).
  6. Système de bioréacteur selon la revendication 5, dans lequel le raccord d'évacuation complémentaire (45) est conçu comme un composant en plusieurs parties.
  7. Système de bioréacteur (1 ; 2 ; 3) destiné à recevoir un sac jetable (44) selon l'une des revendications précédentes, doté d'une plate-forme de travail (60) disposée de manière sensiblement adjacente à une paroi extérieure de la cuve collectrice (10),
    dans lequel une surface de la plateforme de travail (60) accessible par un opérateur (100) est disposée à une hauteur d'environ 80 cm jusqu'à environ 140 cm en dessous d'un bord supérieur de la cuve collectrice (10).
  8. Système de bioréacteur selon la revendication 7, dans lequel la plateforme de travail (60) est conçue de manière à être au moins en partie extensible et/ou pliable.
  9. Système de bioréacteur selon l'une des revendications précédentes, doté d'une cuve collectrice (10) servant à recevoir le sac jetable (44) et d'un bac de récupération (15) disposé en dessous de la cuve collectrice (10) pour recueillir un fluide s'écoulant de la cuve collectrice (10).
  10. Système de bioréacteur selon l'une des revendications précédentes, doté d'un rail de système (17) servant à mettre en place au moins un dispositif auxiliaire.
  11. Système de bioréacteur (1 ; 2 ; 3) destiné à recevoir un sac jetable (44) selon l'une des revendications précédentes, doté d'un chemin de câbles (13) sur une paroi extérieure de la cuve collectrice (10), dans lequel le chemin de câbles (13) est conçu jusqu'à un bord supérieur de la cuve collectrice (10).
  12. Système de bioréacteur selon la revendication 11, dans lequel le chemin de câbles (13) est conçu au moins en partie sous forme de méandres ;
    et/ou
    dans lequel le chemin de câbles (13) s'étend du bord supérieur de la cuve collectrice (10) le long de sa paroi extérieure sensiblement à la verticale vers le bas jusqu'à un point de changement de direction (13A), au niveau duquel le chemin de câbles (13) s'éloigne de la paroi extérieure de la cuve collectrice (10) pour atteindre une zone extérieure du système de bioréacteur (1 ; 2 ; 3).
  13. Système de bioréacteur selon l'une des revendications précédentes, doté d'un dispositif d'obscurcissement (33) d'au moins un hublot (32) et/ou un cache d'obscurcissement pour opacifier une ouverture sur une bord supérieur de la cuve collectrice (10).
  14. Procédé de réception d'un sac jetable (44) dans un système de bioréacteur (1 ; 2 ; 3), présentant les étapes suivantes :
    - la mise à disposition d'un système de bioréacteur (1 ; 2 ; 3) doté d'une cuve collectrice (10), dans la surface de fond (11) de laquelle est constitué un orifice de sortie (5) se rétrécissant vers le bas dans le système de référence terrestre ;
    - la mise à disposition d'un sac jetable (44) doté d'un raccord d'évacuation standard (200) ;
    - la pose d'un raccord d'évacuation (45) complémentaire de l'orifice de sortie (5) sur le raccord d'évacuation standard (200) du sac jetable (44) ;
    - la mise en place du sac jetable (44) dans la cuve collectrice (10) du système de bioréacteur (1 ; 2 ; 3), dans lequel le raccord d'évacuation complémentaire (45) est disposé à l'intérieur de l'orifice de sortie (5).
  15. Procédé selon la revendication 14, dans lequel un tuyau chemine à travers l'orifice de sortie (5), dont une extrémité de tuyau est posée sur le raccord d'évacuation complémentaire (45), dans lequel le raccord d'évacuation complémentaire (45) est guidé dans l'orifice de sortie (5) se rétrécissant vers le bas à l'aide du tuyau.
EP16711523.7A 2015-06-02 2016-03-08 Système de bioréacteur et procédé associé Active EP3303544B1 (fr)

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DE102015007060.6A DE102015007060B4 (de) 2015-06-02 2015-06-02 Bioreaktorsystem und Verfahren
PCT/EP2016/000406 WO2016192823A1 (fr) 2015-06-02 2016-03-08 Système de bioréacteur et procédé associé

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US11649654B2 (en) * 2020-10-12 2023-05-16 Cytiva Us Llc Tank with door locking mechanism
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US11827874B2 (en) 2023-11-28
US20180187140A1 (en) 2018-07-05
US20210139835A1 (en) 2021-05-13
WO2016192823A1 (fr) 2016-12-08
US10947489B2 (en) 2021-03-16
DE102015007060B4 (de) 2023-12-14
DE102015007060A1 (de) 2016-12-08
EP3303544A1 (fr) 2018-04-11

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